tbuckley/cabot-search huggingface dataset:
High complete response rate with TNB-486 in relapsed/refractory follicular lymphoma: Interim results from an ongoing phase 1 study.
Authors: Ranjit Nair, Ryan Jacobs, Seok-Goo Cho, Sumana Devata, Sameh Gaballa, Dok Hyun Yoon, Don A. Stevens, Jin Seok Kim, Nirav Niranjan Shah, Denise Marie Brennan, Jason Law, Rob Chen, Alessandra Forcina, Ben Buelow, Jing-Zhou Hou
Journal: Journal of Clinical Oncology (2023)

7524 Background: Follicular lymphoma (FL) is incurable with a relapsing/remitting pattern and decreasing progression-free survival (PFS) interval per recurrence. In the relapsed/refractory (R/R) setting, patients (pts) failing CAR T or CD20 bispecific T-cell engagers (TCE) have few options. TNB-486 is a novel bispecific CD19xCD3 TCE that induces T-cell–mediated cytotoxicity with reduced cytokine release via a low-affinity αCD3 moiety. We present interim data from a phase 1 dose-escalation study of TNB-486 (NCT04594642). Methods: Third-line+ R/R FL pts (grade [G] 1–3a) were enrolled (prior CD19 therapy allowed). Escalating fixed TNB-486 doses (0.03–2.4 mg) without priming were evaluated prior to implementing single (day [D] 1) and double priming doses (D1 &amp; 8) prior to target dose (D15). TNB-486 was given IV every 2 weeks in 28-d cycles (C) for up to 2 y. Response was assessed with RECIL 2017 by central image review. Adverse events (AEs) and CRS/ICANS were graded by CTCAE v5.0 and 2019 ASTCT criteria. Results: As of Dec 31, 2022, 17 pts received TNB-486 at target doses 0.03–10 mg (median age 68 y [range 33–86]; 53% male; 65% stage III/IV; 25% CD20 − disease; median prior lines of therapy [LOT] 3 [range 2–9]). Prior therapies included αCD20 Ab (100%), alkylator (76%), IMiD (47%), CD20 TCE (12%), CD19 CAR T (12%), and ASCT (6%); 53% progressed or started 2 nd LOT within 24 mo of initiating 1 st LOT (POD24). Median time on study was 7 mo (range 1–22). Eleven pts were response evaluable for efficacy at target doses ≥2.4 mg. Objective response rate (ORR) and complete response (CR) rate were 91% (Table). ORR/CR for pts with CD20 − disease, prior CD20 TCE, and POD24 was 100%. One pt progressed at C6 with preserved CD19 expression; all others remain in remission to date. The 6-mo PFS rate was 91%. No G3+ CRS occurred (59% G1, 12% G2). Neurologic events consistent with ICANS were reported in 24%, all G1–2 except 1 with a G3 event (confusion). All CRS/NT were transient, resolving in a median of 1.5 d (range 1–5). G3+ treatment-related AEs in &gt;10% of pts included decreased lymphocytes (35%) and neutropenia (12%). No treatment-related deaths or AEs leading to discontinuation occurred (1 pt died and 1 discontinued due to COVID-19). One pt received double step-up priming dosing to date with no CRS/NT. Conclusions: TNB-486 induces high complete remission rates during early phase dose escalation. With limited follow-up, responses appear durable in heavily pretreated FL pts, with a manageable safety profile. Dose escalation is ongoing to identify the RP2D. Clinical trial information: NCT04594642 . [Table: see text]
Computational recognition of lncRNA signature of tumor-infiltrating activated CD4+ memory T cells with potential implications in prognosis and immunotherapy of lung adenocarcinoma.
Authors: Shengbo Liu, Qiaxuan Li, Peimeng You, Hongrui Qiu, HaiYu Zhou
Journal: Journal of Clinical Oncology (2023)

e20519 Background: CD4 memory T cells are an important components of the tumour microenvironment and influence tumourigenesis and progression. However, it has not been determined whether lncRNAs in lung adenocarcinoma (LUAD) play a role in activated CD4+ memory T cells (CD4amT). Methods: The LUAD dataset acquired by The Cancer Genome Atlas was used as a training cohort (TCGA-LUAD). For the validation cohort, we used the combination of lung adenocarcinoma datasets from GENE EXPRESSION OMNIBUS database acquired 2 LUAD datasets, and set as the validation cohort (GEO-LUAD). Lung cancer immunotherapy cohorts have been published to test immune responses. The CIBERSORT algorithm was used to assess immune cell infiltration of tumours. Univariate Cox analysis was used to screen for prognostic CD4amT-related lncRNAs (CD4amTRL). LASSO analysis and multivariate Cox analysis were then performed to construct model for prognostic lncRNAs, the effects of which were assessed by Kaplan-Meier curves and subject operating characteristics (ROC). Patients were divided into high and low risk groups based on CD4amTRL signature. We have analyzed differences in enrichment pathways between the two groups and subsequently we investigated genes associated with the cancer-immune process, the immune microenvironment, immunotherapy responses and multiple anti-cancer drug sensitivity correlations. Results: In the two LUAD cohorts, compared with the high infiltration of CD4amT, those in the low infiltration group had better OS benefits (TCGA-LUAD: HR = 0.678; P = 0.028; GEO-LUAD: HR = 0.435; P &lt; 0.0001). We identified 6 prognostic CD4amTRL and constructed prediction models. cd4 CD4amTRL signature distinguished significantly different OS between the high-risk and low-risk groups of TCGA-LUAD (HR = 4.26). The AUCs predicting 1-, 3- and 5-year survival were 0.737, 0.715 and 0.722, respectively. In the GEO-LUAD dataset, the HR was 2.03, while the AUCs predicting 1-, 3- and 5-year survival were 0.719, 0.681 and 0.630, respectively. The risk score model independently predicted OS in LUAD patients and was associated with immune checkpoints. Numerous genes related to the cancer-immune process were highly correlated. In addition, the risk model was significantly associated with multiple immune microenvironment features (p &lt; 0.001). OS was significantly different between the two immunotherapy cohorts in the high- and low-risk groups for CD4amTRL signature (P &lt; 0.001). Conclusions: Our novel risk model developed based on CD4amTRL signatures can aid in predicting clinical prognosis and guiding treatment in patients with LUAD.
Clinical spectrum and outcomes of carbapenem resistant infections in patients with acute leukaemia: A clinical study from a tertiary oncology centre in India.
Authors: Vishnu Hari, N.P. Prakash, Swapna R. Nath
Journal: Journal of Clinical Oncology (2023)

e19020 Background: The prevalence of carbapenem resistant organisms (CRO) are increasing worldwide and associated with grave implications in patients with hematological malignancies. Data on such infections in patients with acute leukemia are scarce, especially from the developing world. The aim of this study was to evaluate characteristics and outcomes of bacteremia with CRO in patients treated for acute leukemia with aggressive chemotherapy regimens. Methods: This prospective observational study was conducted in a tertiary oncology centre in South India. Data on Carbapenem resistant bloodstream infection (CRBSI) in patients with acute leukemia (ALL and AML) aged 14-60 years, from March 2017 to February 2018 were prospectively collected. The final outcome was determined as survival and all-cause death due to CRBSI. Results: Out of 334 patients treated for acute leukemia, 49 patients developed infections with CRO (14.6%). The patients included 27 males (55%) and 22 females (45%), with age ranging from 14 year to 58 years (median age: 42 years). The most common isolates were Klebsiella species (63%) and E.coli (25%). All carbapenem resistant isolates were sensitive to Colistin and 74% were sensitive to Tigecycline. The case-fatality rate was 69% (34/49) in our cohort. Acute kidney injury, shock, septicemia and an initial procalcitonin value &gt; 1mcg/L were predictor of mortality. Disease in remission and neutrophil count recovery post chemotherapy were favorable factors associated with the outcome. There was no statistically significant difference in mortality in patients treated with single agent antibiotics versus combination antibiotics sensitive against CRO. Conclusions: Carbapenem resistant infections in patients with acute leukaemia are associated with a high mortality rate. The factors associated with improved outcome were disease in remission and neutrophil count recovery, post chemotherapy. The presence of acute kidney injury, shock, sepsis and a procalcitonin value more than 1 mcg/L were significant predictor of mortality.
Differential efficacy of tyrosine kinase inhibitors (TKIs) according to the types of EGFR mutations and agents in non-small cell lung cancer (NSCLC): A real-world study.
Authors: Yong Won Choi, Tae-Hwan Kim, Mi Sun Ahn, Hyun Woo Lee, Seok Yun Kang, Jin-Hyuk Choi
Journal: Journal of Clinical Oncology (2023)

e21040 Background: Both 1st and 2nd-generation (gen) EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data about the difference in the efficacy of EGFR-TKIs according to types of EGFR mutations and agents. Methods: This retrospective real-world study evaluated the outcome and clinicopathologic characteristics including the type of EGFR mutations in 237 advanced NSCLC patients (pts) treated with 1st or 2nd-gen (afatinib) EGFR TKIs as first-line therapy. Results: The median progression-free survival (PFS) and overall-survival (OS) of all pts were 11 months (M) and 25M, respectively. In univariate analysis, pts with exon 19 deletion (del) (n = 130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p = 0.047), without difference in PFS (p = 0.138). Pts treated with afatinib (n = 60) showed significant longer median OS compared to those treated with 1st gen TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p = 0.037). In pts with exon 19 del, there was no significant difference in median PFS (p = 0.868) and OS (p = 0.361) between pts treated with afatinib and those with 1st gen TKIs, while significantly better PFS (p = 0.042) and trend in OS (p = 0.069) were observed in pts receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p = 0.028), while age &gt; 70 years (p = 0.017), ECOG performance status ≥2 (p = 0.001), primary metastatic disease (p = 0.007), and synchronous brain metastasis (p = 0.0026) were independent prognostic factors of poor OS. Conclusions: The EGFR exon 19 del was associated with favorable OS in advanced NSCLC pts receiving first-line EGFR TKIs. Moreover, in pts with exon 19 del, first generation TKIs seem to be a reasonable option if osimertinib is unavailable.
Prognostic value of BRAF and RAS mutations in radically resected patients (pts) with stage I-III melanoma: Preliminary results from a retrospective study.
Authors: Sonia Brugnara, Mariacristina Sicher, Salvatore Girlando, Maria Elena Bonandini, Mattia Barbareschi, Michela Frisinghelli, Daniela Mangiola, Orazio Caffo
Journal: Journal of Clinical Oncology (2023)

e21567 Background: Although BRAF and RAS mutations in radically resected pts with stage I- II and III melanoma could have a prognostic value, conflicting evidences are still available. The present retrospective study was aimed to investigate this controversial issue. Methods: We retrospectively evaluated a consecutive series of 201 pts with stage I-III melanoma (AJCC 8th) who have undergone radical surgery from 2005 and 2010. For each pt we retrieved the clinical record and collected data concerning the clinical history. In addition, we evaluated the mutation status of somatic BRAF, KRAS and NRAS on a tissue sample obtained from primary surgery material. We describe the expression rate of such mutations and their relationship with pts’ survival outcomes. Results: To date they are evaluable data on 100 pts (M/F 62/38): the median age was 66 yrs (range 36-91), most of the pts was in stage I-II (66 %). The detected mutations is described in the table. Conclusions: From our preliminary results, it appears that BRAF and RAS mutations did not have prognostic value in the assessed population. The final report of the analyses carried on the whole population will increase the study ability to assess the role of these mutations in predicting the outcomes of radically resected stage I-III melanoma. [Table: see text]
Correlation of survival in colorectal cancer with tumor mutational burden and mutations identified by next-generation sequencing.
Authors: Nicholas Taflin, Lyndsey Sandow, Rajat Thawani, Adel Kardosh, Christopher L. Corless, Emerson Yu-sheng Chen
Journal: Journal of Clinical Oncology (2023)

e18861 Background: Next-generation sequencing (NGS) can identify specific mutations and molecular abnormalities such as high tumor mutational burden (TMB), defined as 10 or more mutations per megabase. Immune checkpoint inhibitors (ICI) have been approved for all solid tumors with high TMB, including colorectal cancer (CRC), though studies have been inconclusive regarding prognosis of high TMB as well as the efficacy of ICI’s in treating CRC specifically. We aimed to use data collected from next-generation sequencing (NGS) of CRC at our institution to correlate survival to TMB, correlate survival to presence of mutations of interest, and to investigate efficacy of ICI in this patient population. Methods: This was a retrospective cohort analysis of patients at a single institution, analyzing NGS of patients who were identified as TMB-high and microsatellite stable (MSS) (n = 161) from January 20218 to December 2020.Demographics, clinical-pathological factors, and NGS results were extracted along with clinical outcomes. We conducted a survival analysis looking at TMB status and selected mutations of interest. A descriptive subset analysis of the patients who underwent treatment with immunotherapy was performed. Results: Patients with high TMB MSS CRC trended to have worse survival with a HR of 1.45, though this was not significant (p = 0.22). Median survival for high TMB patients was 28.1 months and was 77.5 months for non-high TMB. Analysis of NGS revealed 112 unique mutations, with TP53 (82.0%), APC (80.1%), and KRAS (43.5%) occurring the most frequently. Patients were found to have statistically significant worse overall survival with KRAS (HR = 1.81, p = 0.023), CDKN2A (HR = 4.81, p = 0.0002), RB1 (HR = 2.83, p = 0.047), and SMAD4 (HR = 1.858, p = 0.039) mutations. Twelve patients underwent treatment with ICI with nine patients having between 0.7 to 4.1 months of progression-free survival (PFS) and three patients with long PFS of 13.2, 24.7, and 26.3 months. The two patients with the longest PFS were not high TMB. Conclusions: Presence of high TMB in MSS CRC did not show a statistically significant difference in outcome. Presence of KRAS, CDKN2A, RB1, and SMAD4 correlated with significantly worse prognosis. Treatment with ICI’s was effective in some CRC patients though survival did not correlate with high TMB. There is a need to identify a marker beyond TMB which better indicates which patients with MSS CRC will have good response to ICI therapy.
Satisfaction in older patients by geriatric assessment using a novel tablet-based questionnaire system: A cluster-randomized, phase III trial of patients with non–small-cell lung cancer (ENSURE-GA study; NEJ041/CS-Lung001).
Authors: Sayo Soda, Kie Mirokuji, Ryota Saito, Kei Takamura, Ryo Morita, Naoki Furuya, Shoichi Kuyama, Ayako Shiono, Daisuke Arai, Shinobu Hosokawa, Ken Masubuchi, Naoko Matsumoto, Hajime Asahina, Haruka Kondo, Ryoichi Honda, Noboru Hattori, Akihito Yokoyama, Kunihiko Kobayashi, Takeshi Isobe, Yukari Tsubata
Journal: Journal of Clinical Oncology (2023)

12041 Background: To provide optimal treatment for older cancer patients, it is necessary to carry out a geriatric assessment (GA) to evaluate geriatric syndrome. However, GA is not widely performed because it requires expertise. In this ENSURE-GA study, we evaluated if providing a GA summary and recommendations for GA-guided interventions using a novel tablet-based questionnaire system improved satisfaction about communication with physicians for older patients with non-small-cell lung cancer (NSCLC). Methods: Patients with NSCLC who were incapable of radical treatment aged 75 or older were enrolled. All patients underwent a standardized GA using a tablet before starting treatment. Participating institutions were cluster-randomized into the intervention group and the control group. In the intervention group, GA summary and recommendations for GA-guided interventions were immediately returned to guide physicians in selecting treatments and interventions. The control group did not provide a GA summary. The primary outcomes were difference in patient satisfaction pre-treatment and percent change pre- and post-treatment according to the HCCQ questionnaire. Results: A total of 1,021 patients from 78 institutions in Japan were enrolled between 2019–2022. There were no differences in patient backgrounds between the intervention group and the control group: mean age 80.1 yrs. vs. 80.0 yrs.; male 64.1% vs. 66.8%; adenocarcinoma 70.4% vs. 64.8%; and performance status 0-1, 82.4% vs. 79.0%, respectively. All GA domain evaluation results, such as ADL and cognitive function, also did not differ between the two groups. Pre-treatment satisfaction scores were significantly higher in the intervention group than in the control group (29.9 vs. 29.1, p = 0.003). There was no significant difference in the mean percent change between the two groups (-0.13 vs. 2.38, p = 0.165). Conclusions: Providing the oncologist with a GA summary and recommendations for GA-guided interventions improved patient satisfaction from the start of treatment. A novel system using a tablet may be effective at promoting GA more widely. Clinical trial information: UMIN0000037590 .
Role of immunotherapy in stage IV non-small cell lung cancer with liver metastasis: A NCDB analysis.
Authors: Takefumi Komiya, Shinkichi Takamori
Journal: Journal of Clinical Oncology (2023)

9046 Background: Despite approvals of immune checkpoint inhibitors in stage IV non-small cell lung cancer (NSCLC), survival benefit of immunotherapy (IO) in those with liver metastasis is controversial. Randomized controlled trials demonstrated conflicting results. Methods: Using National Cancer Database (NCDB), Stage IV NSCLC cases diagnosed in 2016-2017 with at least 30-day follow up were analyzed. Clinical demographics included age (20-69 vs. 70+), sex (male vs. female), race (whites vs. others), institution (academic vs. others), Charlson-Deyo score (0-1 vs. 2-3), year of diagnosis (2016 vs. 2017), Histology (adenocarcinoma NOS vs. other), brain metastasis (Yes vs. No), bone metastasis (Yes vs. No), liver metastasis (Yes vs. No). They were divided into liver-metastasis positive (LM+) vs. negative (LM-). Information regarding cancer treatment was limited to the first course of therapy, including surgery for primary lesion (Yes vs. No), radiation (Yes vs. No), multi-agent chemotherapy (Yes vs. No), and IO (Yes vs. No). Overall Survival (OS) analysis was performed using Kaplan-Meier curves and Log-rank tests. Cox proportional hazard model was used for multivariate analyses. A two-sided p-value &lt; 0.05 was considered as significant. Results: A total of 13,594 LM+ and 69,885 LM- cases met eligibility and further analyzed. 2,944 and 15,553 patients were treated with IO, respectively. No significant association between use of IO and status of liver metastasis was observed (p = 0.124). The median OS in LM+ cases was significantly shorter than that in LM- cases (5.0 vs 8.8 months, respectively, p &lt; 0.0001). Use of IO was associated with improved OS in both LM+ and LM- cohorts with similar HRs/p-values (0.62/ &lt; 0.0001 and 0.64/ &lt; 0.0001, respectively). Multivariate analysis demonstrated that use of IO had a significantly improved OS in both LM+ (HR = 0.69, p &lt; 0.0001) and LM- (HR = 0.64, p &lt; 0.0001) cohorts. The OS benefit of IO in LM+ cohort remained with propensity score matching analysis (mOS 9.0 vs. 4.4 months, HR = 0.62, p &lt; 0.0001). Further exploratory analysis focusing on those treated with multiagent chemotherapy showed that the addition of IO improved OS in both LM+ (HR = 0.77, p &lt; 0.0001) and LM- (HR = 0.79, p &lt; 0.0001) cohorts. Conclusions: This retrospective study using one of the largest cancer databases suggests that use of IO improves OS of NSCLC patients with LM regardless of chemotherapy status, and its magnitude of OS benefit is similar to that in LM- patients. [Table: see text]
Nivolumab (NIVO) plus relatlimab (RELA) vs NIVO in previously untreated metastatic or unresectable melanoma: 2-year results from RELATIVITY-047.
Authors: Hussein A. Tawbi, F. Stephen Hodi, Evan J. Lipson, Dirk Schadendorf, Paolo Antonio Ascierto, Luis Matamala, Erika Castillo Gutiérrez, Piotr Rutkowski, Helen Gogas, Christopher D. Lao, Juliana Janoski De Menezes, Stéphane Dalle, Ana Maria Arance, Jean-Jacques Grob, Barbara Ratto, Saima Rodriguez, Yuanfang Xu, Sonia Dolfi, Georgina V. Long
Journal: Journal of Clinical Oncology (2023)

9502 Background: In RELATIVITY-047 (NCT03470922), NIVO + RELA demonstrated a statistically significant progression-free survival (PFS) benefit vs NIVO; there was an observed improvement in overall survival (OS) although it was not statistically significant. The combination also had a descriptively higher confirmed objective response rate (ORR) assessed by blinded independent central review (BICR) vs NIVO. Here we report updated descriptive analyses (efficacy, safety, and secondary analyses) with longer (~ 2 years) follow-up. Methods: Patients were randomized 1:1 to receive NIVO 480 mg + RELA 160 mg fixed-dose combination or NIVO 480 mg every 4 weeks, as previously described. Primary endpoint of PFS per RECIST v1.1 was assessed by BICR; secondary endpoints included OS and ORR per BICR. Exploratory analyses were performed for melanoma-specific survival (MSS; defined as death due to melanoma, with censoring of deaths due to other causes) and efficacy outcomes on subsequent systemic therapy. Results: Patients received NIVO + RELA (n = 355) or NIVO (n = 359). Median follow-up was 25.3 months in this updated analysis (minimum follow-up, 21.0 months). NIVO + RELA continued to show a benefit over NIVO for PFS, OS and ORR (Table). A similar improvement was also observed in MSS. NIVO + RELA was generally favored over NIVO across key subgroups (consistent with previous reports). Subsequent systemic therapy was received by 131 (36.9%) and 136 (37.9%) patients in the NIVO + RELA and NIVO arms, respectively. Treatment-related adverse events (TRAEs; any grade) leading to treatment discontinuation were observed in 61 (17.2%) and 31 (8.6%) patients on NIVO + RELA and NIVO, respectively. Grade 3–4 TRAEs were observed in 78 (22.0%) patients on NIVO + RELA and 43 (12.0%) patients on NIVO. In total, there were 6 treatment-related deaths (NIVO + RELA, n = 4; NIVO, n = 2); no new treatment-related deaths have been reported since the last analysis. Conclusions: With 12.3 months of additional follow-up, a consistent benefit was observed with NIVO + RELA vs NIVO for PFS, OS and ORR in the ITT population, as well as in key patient subgroups. MSS was longer with NIVO + RELA compared with NIVO. The safety profile of NIVO + RELA remained consistent with previous reports, with no new or unexpected safety signals. Efficacy outcomes on subsequent systemic therapy (by type of subsequent therapy, including PD-L1/CTLA-4) will be presented. Clinical trial information: NCT03470922 . [Table: see text]